Diffuse Large B Cell Lymphoma Most Frequently Diagnosed Subtype

The most frequently diagnosed subtype of non-Hodgkin's lymphoma is diffuse large B-cell lymphoma (DLBCL).

This aggressive lymphoma subtype is curable in about half the cases when treated with frontline combination chemotherapy, such as R-CHOP or DA-EPOCH.

In recent years researchers determined that because DLBCL patients have responded very differently over the years to treatment regimens, certain subtypes of DLBCL could be found if studied at the molecular level. To that end, they found three distinct subtypes.

Germinal Center B-Cell-like Diffuse Large B Cell Lymphoma (GCB DLBCL)

GCB DLBCL represents the most commonly diagnosed subtype of DLBCL. In general, patients with this subtype have a better prognosis compared to other subtypes.

This subtype is often characterized by a mutated or translocated BCL-6 gene. It has also been found to be sensitive to inhibition of topoisomerase II.

In addition to the standard chemotherapy regimen R-CHOP, the use of topoisomerase II inhibitors like etoposide and doxorubicin in such regimens as CHOEP and DA-EPOCH-R has shown to be effective against this disease.

Activated B Cell-like Diffuse Large B Cell Lymphoma (ABC DLBCL)

This subtype of diffuse large B cell lymphoma (DLBCL) is associated with poorer patient outcomes compared with GBC DLBCL, and it has been determined that patients with this subtype do not respond well to the otherwise popular R-CHOP regimen.

ABC DLBCL is characterized by the activation of NF-kB genes. Studies have shown that this subtype especially sensitive to inhibiting the IkB kinase, which activates the NF-kB genes.

Bortezomib (sold as Velcade) is a proteasome inhibitor that leads to the inhibition of these activated genes. It has thus been studied as a treatment option when combined with DA-EPOCH in patients whose molecular subtype of DLBCL has been determined prior to treatment to be ABC DLBCL.

Other ongoing studies are exploring whether bortezomib plus R-CHOP will be as effective against ABC DLBCL.

Other individual drugs that have shown some promise in the treatment of this subtype include the immunomodulatory drug lenalidomide (Revlimid), the BTK inhibitor ibrutinib (Imbruvica), the protein kinase C beta inhibitor enzastaurin and the bcl-2 inhibitor navitoclax.

Primary Mediastinal B-cell Lymphoma (PMBL)

PMBL is the oddball of this group. It represents about 10 percent of DLBCL diagnoses, derives from a thymic B-cell in the mediastinum (a general area within the chest that includes the heart, esophagus, trachea, etc), and in fact has a molecular profile that is considered to more closely resemble classical Hodgkin's lymphoma than either of the previously listed subtypes.

Additionally, PMBL tends to be diagnosed in girls and young women.

Most often, this subtype is treated with the combination chemotherapy regimen MACOP-B (methotrexate, leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin). Radiation to the chest was and still sometimes is part of the treatment and combined with combination chemotherapy, but some studies show that the radiation causes too many problems down the road in patients that are otherwise cured of the disease. For that reason, researchers have explored the use of DA-EPOCH-R in these patients with the hope that this regimen can eliminate the need for radiotherapy.

Despite the rarity of this diagnosis and the lack of a whole lot of literature on the disease, PMBL has been shown to be the most treatable subtype of DLBCL, with high cure rates.

Sources:
Cancer Network: Appropriate Management of Molecular Subtypes of Diffuse Large B-Cell Lymphoma
National Cancer Institute
Cancer Treatment.net